Memory CD4+ T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms underlying the generation and maintenance of immunological memory. In 2011, we identified a highly pathogenic IL-5-producing memory Th2 cell subset in allergic airway inflammation. Based on these data, we propose a new model called “Pathogenic Th population disease induction model” in the pathogenesis of Th1/Th2/Th17 diseases (Nakayama et al. Ann. Rev. Immunol. 2017). We have extended our research, and found that the pathogenic Th2 cells (Tpath2 cells) are a distinct cell population generated in vivo, and express high levels of IL-33 receptor component, ST2 (Endo et al. Immunity, 2015). These newly identified memory type Tpath2 cells are CD44+ CD62Llo CXCR3lo CCR4+ CCR8+ IL-7Ra+ ST2+ CD4 T cells. A similar Tpath2 cells were identified in the patients of eosinophilic esophagitis and atopic dermatitis (Prussin et al JACI 2016). More recently, we identified the functional ligand for CD69 that is expressed on the pathogenic T cells. In lymphoid tissues, CD69 regulates cellular retention via inhibition of S1P1 expression and requires no specific ligands to function. In contrast, we identified that myosin light chain (Myl) 9 and 12 are new functional ligands for CD69. Within inflamed mouse and human airways, platelet-derived Myl9/12 localize on the luminal surface of blood vessels and form intravascular net-like structures. Moreover, blockade of the CD69-Myl9/12 interaction ameliorates allergic airway inflammation (Hayashizaki et al. Science Immunol, 2016, Kimura et al. Immunological Reviews, 2017). Thus, the Myl9/12-CD69 interaction is a key event in the recruitment of activated lymphocytes in inflamed tissues and could be a therapeutic target for intractable airway inflammatory diseases.